Two low molecular weight oliogonucleotides were identified in this laboratory that, among cellular protein kinases, specifically inhibit those of nuclear provenance. In addition, they block the phosphoryl transfer from ATP to suitable acceptor proteins catalyzed by protein kinases associated with the transforming proteins of several RNA-tumor viruses. The oligonucleotide inhibitors will be purified to homogeneity and their structure will be determined by sequence analysis and by identification of their termini. Their mode of action in vitro will be studied by kinetic analyses. Preliminary data show that there are proteins whose phosphorylation is specifically inhibited by the oligonucleotides when phosphorylations are carried out in crude subcellular fractions. Attempts will be made to identify these proteins.